What is the Histological Classification of Lymphogranulomatosis?
There are 4 histological types of lymphogranulomatosis: lymphohistiocytic (lymphoid predominance), nodular sclerosis, mixed cell and lymphoid depletion.
With this pathology, there are no pronounced foci of sclerosis and necrosis. Berezovsky-Sternberg cells are also not numerous. In the event that they are determined, then these are not typical “diagnostic” forms.
Nodular sclerosis is accompanied by the formation of regular collagen cords, which divide the formed tumor tissue into many areas of a rounded shape.
According to its morphology, the mixed cell variant of lymphogranulomatosis is closer to the classical description of Sternberg.
Symptoms of Histological Classification of Lymphogranulomatosis
The clinical picture of the disease is extremely diverse.
Initially, the disease develops in the lymph nodes, while the pathological process spreads to most organs, this disease is accompanied by symptoms of intoxication. The main clinic of the disease determines the defeat of the internal organs. The first symptom of lymphogranulomatosis is swollen lymph nodes. As a rule, a pathological process develops in the cervical lymph nodes.
These lymph nodes are mobile, have a tight-elastic consistency, are not fused to the skin, soreness on palpation is extremely rare. As the pathological process develops, the enlarged lymph nodes merge into large conglomerates.
Some patients have enlarged lymph nodes of the mediastinum. Typically, such an increase is detected by chance during fluorography. It is also possible that the clinical picture appears in the later stages of conglomerate development, which is accompanied by cough, shortness of breath and symptoms of compression of the superior vena cava.
In some cases, the disease develops sharply, patients complain of an increase in body temperature, a rapid decrease in body weight. Typically, an increase in lymph nodes in this disease is noted later.
Laboratory signs of pathology are leukopenia and anemia.
In the period of the height of the disease, damage to all lymphoid organs is noted, also almost all organs and systems are involved in the pathological process, while damage to the spleen occurs in 30% of patients.
Also quite often the lungs are affected. Quite often, with lymphogranulomatosis, fluid accumulation in the pleural cavities is detected. As a rule, this lesion is detected by x-ray examination.
The development of a tumor from the lymph nodes is usually infiltrative, grows in the heart, esophagus, trachea.
With the same frequency as with a lung lesion, a lesion of the skeletal system appears in the pathology, the most frequently affected bones are the vertebrae, sternum, pelvic bones, and ribs.
It is worth noting that the first symptoms of bone damage are intense pain. Rarely enough, bone damage is the first visible sign of lymphogranulomatosis.
Damage to the liver is usually accompanied by increased activity of alkaline phosphatase, serum albumin is also reduced.
The gastrointestinal tract is usually involved a second time in the pathological process, as a result of compression or germination of the tumor from the affected lymph nodes.
Very rarely observed lymphogranulomatous lesion of the stomach, as well as the small intestine.
Among other lesions, lesions of the central nervous system, usually the spinal cord, are noted. Pathological foci are located in the meninges, leading to serious neurological disorders. Another quite often involved organ in this disease is the skin.
Half of patients have moderate neutrophilic leukocytosis. In the later stages, lymphocytopenia is usually observed. In 0.5-3% of patients with lymphogranulomatosis, high eosinophilia is detected (up to 80%), in 10-15% of exacerbations are accompanied by an increase in the number of platelets (up to 6 × 105 in 1 μl). Anemia, leukopenia, thrombocytopenia with hemorrhagic diathesis are not uncommon in the late stages of the disease and are more often the result of intensive radiation and chemotherapy.
Acceleration of ESR is a nonspecific symptom in lymphogranulomatosis, which is quite sensitive to the activity of the process (except for the terminal period). An increase in ESR is associated with an increase in the content of a1– and especially a2-globulin (due to ceruloplasmin and haptoglobin) and fibrinogen.
The myelogram in patients with lymphogranulomatosis, as a rule, does not have significant deviations from the norm, but a bone marrow examination in some cases reveals a characteristic morphological picture of lymphogranulomatosis.
The modern clinical classification of lymphogranulomatosis is based on the gradual spread of the disease from the primary focus to neighboring areas of the lymphatic system. She divides lymphogranulomatosis into 4 stages. Each stage is divided into two subgroups, depending on the absence (A) or the presence (B) of one or more common symptoms of the disease.
Clinical classification of lymphogranulomatosis
Stage I. Damage to the lymph nodes of one area (I) or damage to one extra lymphatic organ or localization (IE1).
Stage II. The defeat of the lymph nodes of two regions or more on one side of the diaphragm (II) or the same and local lesion of one extra lymphatic organ or spread (IIE) on the same side of the diaphragm.
The number of affected areas (localizations) of the lymph nodes is indicated by the Arabic numeral: II2, II3.
Stage III. The defeat of the lymph nodes of any areas on both sides of the diaphragm (III), accompanied by either a local lesion of one extra-lymphatic organ, or spread (IIIE), or a lesion of the spleen (IIIS), or a lesion of both (IIIES).
Stage IV. Diffuse lesion of one or more organs with or without lymph nodes.
The localization of the lesion in stage IV, proven histologically, is indicated by the symbols: L – lungs, H – liver, M – bone marrow, O – bones, P – pleura, D – skin, subcutaneous tissue. Damage to the liver and bone marrow is always stage IV.
General symptoms (B).
- Night sweats.
- Temperature above 38 ° C.
- Weight loss of 10% or more in 6 months.
Lymphatic organs: lymph nodes, spleen, thymus, Waldeyer-Pirogov ring.
The course of lymphogranulomatosis is very diverse – from benign, lasting for many years, to subacute, leading patients to death in a few months. When determining the prognosis, the sex of the patient should be taken into account (in men, lymphogranulomatosis is usually heavier), age (the prognosis is worse in children and the elderly), the stage of the disease, the histological variant, and the severity of general symptoms. Survival of patients is largely determined by the presence or absence of common symptoms. Without intoxication, the disease can be indefinitely long, with its appearance, the prognosis sharply worsens, life expectancy is limited to one or several years.
The early signs of an unfavorable course of the disease are biological indicators of activity:
- ESR acceleration of more than 30 mm / h;
- increased fibrinogen concentration of more than 5.0 g / l;
- increased concentration of a2-globulin more than 10 g / l;
- an increase in the concentration of haptoglobin more than 1.5 mg%;
- increasing the concentration of ceruloplasmin more than 0.4 units of extinction.
If at least 2 of these 5 indicators exceed the indicated levels, then the biological activity of the process is stated (it is indicated in the diagnosis by the letter b – II Ab).
The appearance of these signs of activity during the period of remission usually indicates a beginning exacerbation.
Lymphogranulomatosis can be complicated by acute asphyxia (with a rapid increase in the lymph nodes of the mediastinum), compression of the bile duct with the development of obstructive jaundice, intestinal obstruction (when the intestines are compressed by the lymph nodes), and the formation of fistulas of enlarged peripheral lymph nodes. The most formidable complication is a violation of the protein metabolism of the kidneys and intestines. As a rule, it quickly leads to the death of the patient.
Pregnancy adversely affects the course of lymphogranulomatosis. Preserving pregnancy prevents timely examination and treatment. Exacerbations during pregnancy occur in 63% of cases.
During the course of the disease, insolation, physiotherapeutic procedures (quartz, UHF, galvanization, dirt) are negatively reflected. The cause of death of most patients with lymphogranulomatosis is the progression of the disease, leading to cachexia, pulmonary-cardiac, hepatic, hepatic-renal failure, impaired protein metabolism. In 25% of cases, complications of treatment lead to death: hematopoiesis, purulent infections, bleeding, secondary malignant neoplasms. Patients with lymphoid predominance and nodular sclerosis usually die from treatment complications, and patients with the option of lymphoid depletion, as a rule, die directly from the progression of the disease.
Lymphogranulomatosis is characterized by an immune defect in the form of sharp inhibition or loss of delayed skin reactions. This defect is manifested by negative results of skin tests with tuberculin, with dinitrochlorobenzene, late rejection of the transplanted skin flap. The defect appears in untreated patients with the initial stages of lymphogranulomatosis and increases with the development of the disease, especially with the addition of common symptoms. However, the ability to form antibodies in lymphogranulomatosis is preserved, decreasing only in the terminal period.
An immune defect in lymphogranulomatosis is associated with a dysfunction of T-lymphocytes, but there is no direct correlation between the total number of lymphocytes and an immune defect. An increase in the number of T-suppressors producing prostaglandins was found, which leads to immunological hyporeactivity. In addition, antibodies fixed on T-lymphocytes and suppressing their functional ability were detected. Immunological changes in lymphogranulomatosis are characterized by a greater predisposition of patients to tuberculosis, viral diseases, such as shingles, measles, chickenpox, hepatitis.
During cytogenetic studies of the material of the affected lymph nodes, more than half of patients with lymphogranulomatosis show violations of the karyotype – lines of abnormal polyploid cells, often with different chromosomal markers. Cytogenetic study of Berezovsky-Sternberg cells revealed marker chromosomes in 1 out of 8 cases, proving the monoclonal origin of this cell.
Treatment of Histological Classification of Lymphogranulomatosis
In recent years, due to the increase in the number of patients with lymphogranulomatosis who received radiation therapy, more and more attention is paid to late radiation injuries: pneumonitis, pericarditis, crippling fibrosis of the subcutaneous tissue, damage to the nervous system. An increase in late complications forces us to look for new methods of radiation therapy, to reduce radiation doses as a result of a combination with chemotherapy.
Chemotherapy. Monochemotherapy – the isolated use of vinblastine, natulan, chlorobutin and other drugs – is rarely used either in elderly patients or in many treated patients with hematopoietic hypoplasia.
The method of treatment of the primary patient with lymphogranulomatosis is chosen depending on the stage, histological option, the presence or absence of common symptoms.
Currently, radical radiation therapy is considered the method of choice for patients with IA – IIA stages. However, the use of polychemotherapy according to the MOPP scheme in these stages gives equally good results. Polychemotherapy in patients with stages I – II makes a diagnostic examination of the abdominal cavity not always necessary.
For patients with P>, IIB, IIIA, IIIB and IVA stages, it is preferable to prescribe combined (polychemio and radiation) therapy. More often MORP or its variants are used, the number of cycles is not less than 3. There are various options for radiation therapy – from local exposure of primary lesions in reduced doses to radical (3 stages) with irradiation of extralymphatic lesions in stage IVA. It should be borne in mind that adverse histological variants of lymphogranulomatosis require large doses of radiation exposure. Patients with symptoms of intoxication after the end of radiation therapy spend at least 3 consecutive cycles of chemotherapy.
As a supportive treatment, re-induction cycles of drug complexes can be used every 2, 4, 6 months for 3 years; you can use vinblastine. The attitude to supportive treatment is ambiguous in various centers for the treatment of lymphogranulomatosis.
In the IVB stage, cyclic chemotherapy is indicated with subsequent support of remission in cases of its achievement. Perhaps the addition of chemotherapy with local exposure to individual process locations. After radical exposure, 10-30% of patients with stages IA – IIA and 30-60% with stages IIB – IV after combined chemotherapy have exacerbated the disease in a period of several months to several years. The number of exacerbations is not associated with the histological type, the largest number of exacerbations is found with nodular sclerosis. The life expectancy of patients with lymphogranulomatosis is affected by the presence or absence of symptoms of intoxication; this is best demonstrated by patients with stage II of the process.
There are several approaches to the problem of recurrence of lymphogranulomatosis.
- Maintenance of improvement conditions to reduce the number of patients with exacerbations. There are chemotherapy regimens for up to 2 years with the use of several chemotherapeutic complexes alternating every month. Intensive treatment during the improvement period increases the number of late complications and reduces the possibility of treating exacerbations.
- Development of “rescue therapy” methods in cases of exacerbations after relatively sparing induction therapy. The results of cyclic chemotherapy for exacerbations after radical exposure (at stages I – II) are slightly inferior to the results of polychemotherapy of primary patients. It is difficult to treat exacerbations in patients with stages III – IV. The effectiveness of the primary treatment or the development of exacerbation during the first year requires a change in the complex of chemotherapy drugs.
The most widespread is the sequence of treatment regimens: MOPP -> ABVD —► SCAB (or ABDIC).
Intensification of treatment, lengthening the life of patients with lymphogranulomatosis lead to an increase in late treatment complications. Infertility occurs in all men and in 50% of women who received treatment according to the MPP scheme. It is found much less frequently when using other complexes of drugs. In patients with lymphogranulomatosis 2-8 years after the end of treatment (especially combined), the number of acute myeloid leukemia increases.
At stage IAa, 2 courses of polychemotherapy are carried out and then a radical radiation program is carried out, after which 4 courses of polychemotherapy are carried out. Removal of the spleen during stage IAa is not strictly necessary. With IB, II, III stages, splenectomy is required. In stages IB – III, 2-3 courses of polychemotherapy are carried out (it is advisable to alternate courses of CORR and CHOP or CORR and MORP; this alternation is especially important when the effect of the performed chemotherapy regimen is incomplete), then a radical radiation program is prescribed, after which 3-4 cycles of polychemotherapy are carried out (preferably with alternating circuits).
There are no strict programs for therapy in stage IV, but the principle of radicalism even in this stage allows us to achieve recovery in 25% of cases. In case of damage to lung tissue, it is desirable to remove the lobe together with the tumor focus, as well as the lymph nodes of the root of the lung (mediastinum). When the spinal cord is compressed, the patient is irradiated with the affected area at a dose of up to 45-50 Gy, including one segment located above and below the intended focus in the irradiation zone. With local liver damage in the case of ineffectiveness of polychemotherapy, local radiation can be carried out in a dose of up to 30 Gy. However, often with stage IV of the process, local therapy is impossible due to the prevalence of the lesion; therefore, the main is polychemotherapy – 10-12 courses of alternating regimens.
With a relapse of lymphogranulomatosis, if the process is local and accessible for surgical intervention, a biopsy with extirpation of the entire group of enlarged lymph nodes is necessary (you must always bear in mind the possibility of the patient developing another tumor). In case of local recurrence, its zone is then irradiated at a dose of 45 Gy and adjacent zones of the lymph nodes at a dose of 40 Gy. In the future, 6 courses of alternating chemotherapy regimens are given.